Alzheimer's & dementia (Amsterdam, Netherlands) · 2026
Brain atrophy and clinical diagnosis independently predict default mode network failure across the Alzheimer's disease continuum.
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Alghamdi Mohammed, von Wegner Frederic, Chan Daniel Kam Yin, Green Michael, Alzheimer's Disease Neuroimaging Initiative
Аннотация
INTRODUCTION: This study examined the link between default mode network (DMN) functional connectivity, cerebral small vessel disease (CSVD), brain atrophy, and plasma Alzheimer's disease (AD) biomarkers.
METHODS: We analyzed the Alzheimer's Disease Neuroimaging Initiative database (N = 279), examining the relationships between DMN functional integrity (network failure quotient [NFQ]), gray and white matter fractions (GMF, WMF), white matter hyperintensities (WMHs), plasma phosphorylated tau (p-tau)217 and amyloid beta (Aβ)42/Aβ40 ratio, and clinical assessments. Statistical associations were tested using one-way analysis of variance and univariate and multivariate regression models.
RESULTS: The AD group showed increased NFQ values (P < 0.001). Significant univariate associations were found between NFQ and WMH, gray and white matter atrophy, Aβ ratio, and p-tau217 (P < 0.05). Atrophy markers (GMF, WMF) and AD diagnosis were the only independent predictors of NFQ in multivariate models (P < 0.05).
DISCUSSION: Our study identifies markers of brain atrophy as independent predictors of DMN failure, unlike AD plasma biomarkers and magnetic resonance imaging markers of CSVD.
METHODS: We analyzed the Alzheimer's Disease Neuroimaging Initiative database (N = 279), examining the relationships between DMN functional integrity (network failure quotient [NFQ]), gray and white matter fractions (GMF, WMF), white matter hyperintensities (WMHs), plasma phosphorylated tau (p-tau)217 and amyloid beta (Aβ)42/Aβ40 ratio, and clinical assessments. Statistical associations were tested using one-way analysis of variance and univariate and multivariate regression models.
RESULTS: The AD group showed increased NFQ values (P < 0.001). Significant univariate associations were found between NFQ and WMH, gray and white matter atrophy, Aβ ratio, and p-tau217 (P < 0.05). Atrophy markers (GMF, WMF) and AD diagnosis were the only independent predictors of NFQ in multivariate models (P < 0.05).
DISCUSSION: Our study identifies markers of brain atrophy as independent predictors of DMN failure, unlike AD plasma biomarkers and magnetic resonance imaging markers of CSVD.